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Hydrogen peroxide produced by oral Streptococci induces macrophage cell death.

Okahashi N, Nakata M, Sumitomo T, Terao Y, Kawabata S - PLoS ONE (2013)

Bottom Line: Although the cytotoxicity of H2O2 has been widely recognized, the effects of H2O2 produced by oral streptococci on host defense systems remain unknown.Catalase, an enzyme that catalyzes the decomposition of H2O2, inhibited the cytotoxic effect of S. oralis.Furthermore, H2O2 alone was capable of inducing cell death.

View Article: PubMed Central - PubMed

Affiliation: Department of Oral Frontier Biology, Osaka University Graduate School of Dentistry, Suita-Osaka, Japan. okahashi@dent.osaka-u.ac.jp

ABSTRACT
Hydrogen peroxide (H2O2) produced by members of the mitis group of oral streptococci plays important roles in microbial communities such as oral biofilms. Although the cytotoxicity of H2O2 has been widely recognized, the effects of H2O2 produced by oral streptococci on host defense systems remain unknown. In the present study, we investigated the effect of H2O2 produced by Streptococcus oralis on human macrophage cell death. Infection by S. oralis was found to stimulate cell death of a THP-1 human macrophage cell line at multiplicities of infection greater than 100. Catalase, an enzyme that catalyzes the decomposition of H2O2, inhibited the cytotoxic effect of S. oralis. S. oralis deletion mutants lacking the spxB gene, which encodes pyruvate oxidase, and are therefore deficient in H2O2 production, showed reduced cytotoxicity toward THP-1 macrophages. Furthermore, H2O2 alone was capable of inducing cell death. The cytotoxic effect seemed to be independent of inflammatory responses, because H2O2 was not a potent stimulator of tumor necrosis factor-α production in macrophages. These results indicate that streptococcal H2O2 plays a role as a cytotoxin, and is implicated in the cell death of infected human macrophages.

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Induction of TNF-α by S. oralis spxB KO mutant.Differentiated THP-1 macrophages were infected with viable S. oralis strains for 2 h, and then washed and cultured for additional 18 h. Other cultures were stimulated by exposure to H2O2. The release of TNF-α was determined using an ELISA kit. Data are shown as the mean ± SD of triplicate samples. *p<0.05 as compared with untreated control (None).
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pone-0062563-g007: Induction of TNF-α by S. oralis spxB KO mutant.Differentiated THP-1 macrophages were infected with viable S. oralis strains for 2 h, and then washed and cultured for additional 18 h. Other cultures were stimulated by exposure to H2O2. The release of TNF-α was determined using an ELISA kit. Data are shown as the mean ± SD of triplicate samples. *p<0.05 as compared with untreated control (None).

Mentions: It is widely recognized that microbial stimulation induces cytokine production in macrophages. Infection with viable S. oralis WT strain induced the production of an inflammatory cytokine, TNF-α (Figure 7). The amount of TNF-α in macrophage culture supernatants increased in a dose-dependent manner. No significant differences in cytokine production between macrophages infected with either WT or spxB Rev strains and those infected with spxB KO mutants were observed. Furthermore, H2O2 on its own had a limited stimulatory effect on TNF-α production (Figure 7). These results suggest that H2O2 is not essential to TNF-α production in S. oralis-infected macrophages.


Hydrogen peroxide produced by oral Streptococci induces macrophage cell death.

Okahashi N, Nakata M, Sumitomo T, Terao Y, Kawabata S - PLoS ONE (2013)

Induction of TNF-α by S. oralis spxB KO mutant.Differentiated THP-1 macrophages were infected with viable S. oralis strains for 2 h, and then washed and cultured for additional 18 h. Other cultures were stimulated by exposure to H2O2. The release of TNF-α was determined using an ELISA kit. Data are shown as the mean ± SD of triplicate samples. *p<0.05 as compared with untreated control (None).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3643943&req=5

pone-0062563-g007: Induction of TNF-α by S. oralis spxB KO mutant.Differentiated THP-1 macrophages were infected with viable S. oralis strains for 2 h, and then washed and cultured for additional 18 h. Other cultures were stimulated by exposure to H2O2. The release of TNF-α was determined using an ELISA kit. Data are shown as the mean ± SD of triplicate samples. *p<0.05 as compared with untreated control (None).
Mentions: It is widely recognized that microbial stimulation induces cytokine production in macrophages. Infection with viable S. oralis WT strain induced the production of an inflammatory cytokine, TNF-α (Figure 7). The amount of TNF-α in macrophage culture supernatants increased in a dose-dependent manner. No significant differences in cytokine production between macrophages infected with either WT or spxB Rev strains and those infected with spxB KO mutants were observed. Furthermore, H2O2 on its own had a limited stimulatory effect on TNF-α production (Figure 7). These results suggest that H2O2 is not essential to TNF-α production in S. oralis-infected macrophages.

Bottom Line: Although the cytotoxicity of H2O2 has been widely recognized, the effects of H2O2 produced by oral streptococci on host defense systems remain unknown.Catalase, an enzyme that catalyzes the decomposition of H2O2, inhibited the cytotoxic effect of S. oralis.Furthermore, H2O2 alone was capable of inducing cell death.

View Article: PubMed Central - PubMed

Affiliation: Department of Oral Frontier Biology, Osaka University Graduate School of Dentistry, Suita-Osaka, Japan. okahashi@dent.osaka-u.ac.jp

ABSTRACT
Hydrogen peroxide (H2O2) produced by members of the mitis group of oral streptococci plays important roles in microbial communities such as oral biofilms. Although the cytotoxicity of H2O2 has been widely recognized, the effects of H2O2 produced by oral streptococci on host defense systems remain unknown. In the present study, we investigated the effect of H2O2 produced by Streptococcus oralis on human macrophage cell death. Infection by S. oralis was found to stimulate cell death of a THP-1 human macrophage cell line at multiplicities of infection greater than 100. Catalase, an enzyme that catalyzes the decomposition of H2O2, inhibited the cytotoxic effect of S. oralis. S. oralis deletion mutants lacking the spxB gene, which encodes pyruvate oxidase, and are therefore deficient in H2O2 production, showed reduced cytotoxicity toward THP-1 macrophages. Furthermore, H2O2 alone was capable of inducing cell death. The cytotoxic effect seemed to be independent of inflammatory responses, because H2O2 was not a potent stimulator of tumor necrosis factor-α production in macrophages. These results indicate that streptococcal H2O2 plays a role as a cytotoxin, and is implicated in the cell death of infected human macrophages.

Show MeSH
Related in: MedlinePlus